Esters of bi- and tricyclic amino alcohols and their use in pharmaceutical compositions

ABSTRACT

The new compounds of formula 
     
         A--O--CO--Z                                                (I) 
    
     (wherein A and Z are defined as explained in the specification) can be prepared by conventional methods; they are suitable as active substances for pharmaceutical compositions.

This is a continuation of application Ser. No. 08/117,199, filed Dec. 2, 1993, now abandoned.

The invention relates to new esters of bi- and tricyclic amino alcohols, the preparation of these compounds and their use in pharmaceutical compositions.

The new compounds correspond to the formula

    A--O--CO--Z                                                (I)

wherein

A represents the group ##STR1## wherein

m represents 0, 1 or 2,

n represents 1 or 2 and m+n≦3,

Q represents one of the double-bonded groups --CH₂ --CH₂ --, --CH₂ --CH₂ --CH₂ --, --CH═CH--, ##STR2##

or --CH₂ --Q"--(CH₂)_(p) --(P=0 or 1)

and

Q' represents the group ═NR, the group ═NRR' or the group CH₂, wherein R represents an optionally halo- or hydroxy-substituted C₁₋₄ -alkyl group, R' represents a C₁₋₄ -alkyl group and R and R' together may also form a C₄₋₆ -alkylene group, and, in the case of quaternary compounds, an equivalent of an anion (X.sup.⊖), is associated with the positive charge of the N-atom,

and

Q" has the same meanings as Q', with the exception of CH₂, and with the proviso that Q represents --CH₂ --Q"--(CH₂)_(p) -- when Q' represents CH₂,

represents the group ##STR3## wherein

R₁ represents H, OH, CH₂ OH, C₁₋₄ -alkyl or C₁₋₄ -alkoxy,

R₂ and R₃, which may be identical or different and one of which may also be H, represent

(a) phenyl, furyl, an aromatic group which is isoelectronic with thienyl, C₅₋₇ -cycloalkyl, pyridyl, C₅₋₇ -cycloalkenyl or, in particular if m is equal to 0 and/or Q is equal to --CH₂ --Q"--(CH₂)_(p), R₂ may also represent thienyl,

(b) an aliphatic group having up to 20 carbon atoms optionally interrupted by oxygen, or a C₁₋₆ -alkyl group substituted by phenyl, phenoxy, thienyl, furyl, C₅₋₇ -cycloalkyl or fluorine,

(c) the entire group III may also represent the tricyclic group of the formula ##STR4## or a group of formula ##STR5## wherein B may represent S or CH═CH, R'₁ has the same meaning as R₁ and may additionally represent phenyl, thienyl, furyl, thiazolyl, thiadiazolyl or methoxyphenyl, Y represents a single bond, an O- or S-atom or one of the groups --CH2--, --CH₂ --CH₂ --, --CH═CH--, --OCH₂ -- or --S--CH₂ -- and q represents 1, 2 or 3.

In the compounds of formula I R₂ preferably represents OH. The group --OA preferably has an α-configuration and is derived for example from scopine, tropine, granatoline or 6,7-dehydrotropine or the corresponding nor-compounds; --OA may, however, also have the β-configuration as in pseudotropine or pseudoscopine.

Examples of corresponding groups include: ##STR6##

The substituent R is preferably a lower alkyl group, especially CH₃, or may also represent, for example, C₂ H₅, n--C₃ H₇, i--C₃ H₇ and R' preferably represents CH₃. R and R' together may represent, for example, --(CH₂)₅ --. The halogen substituent for R is preferably F or, to a lesser extent, Cl. If R represents a halo- or hydroxy-substituted alkyl group it is preferably --CH₂ --CH₂ F or --CH₂ --CH₂ OH. Accordingly, the group A represents, for example, the groups of scopine, N-ethylnorscopine, N-isopropylnorscopine, tropine, N-isopropylnortropine, 6,7-dehydrotropine, N-β-fluoroethylnortropine, N-isopropyl-6,7-dehydronortropine, N-methylgranatoline or the corresponding quaternary compounds, the anion preferably being Br.sup.⊖ or CH₃ SO.sup.⊖₃.

The group Z may have the following meanings, for example, whilst the aromatic groups may also be substituted, e.g. by CH₃, OCH₃, F or Cl: ##STR7##

If in the group II m represents O and/or Q represents --CH₂ --Q"--(CH₂)_(p) --, the group III may have the following additional meanings, in particular: ##STR8##

The quaternary compounds of formula I are particularly suitable for therapeutic use, while the tertiary compounds are important not only as active substances but also as intermediate products.

The compounds according to the invention are anticholinergics with a potent and long-lasting effect. At dosages in the microgram range, periods of effect of more than 24 hours are achieved after inhalation. Moreover, the toxicity is in the same range as that of the standard commercial product ipratropium bromide, whilst at the same time the therapeutic effect is in some cases significantly greater.

In accordance with their nature as anticholinergics, the new compounds are suitable, for example, for treating chronically obstructive bronchitis and (slight to moderate) asthma and also for treating vagally induced sinus bradycardia. Whereas in diseases of the respiratory tract it is chiefly recommended to administer the new active substances by inhalation (especially the quaternary compounds), thereby largely eliminating any side effects, the compounds are preferably administered by intravenous or oral route in the case of sinus bradycardia. It has been found to be advantageous that the new compounds have virtually no effect on gastrointestinal motility.

For use, the compounds according to the invention are processed with known excipients and/or carriers to form conventional galenic preparations, e.g. solutions for inhalation, suspensions in liquefied propellant gases, preparations containing liposomes or proliposomes, injectable solutions, plain or coated tablets, capsules, powders for inhalation for use in conventional inhalers.

Examples of formulations (amounts given in percent by weight):

1. Metering aerosol

    ______________________________________                                         Active substance according to                                                                           0.005                                                 the invention                                                                  Sorbitantrioleate        0.1                                                   Monofluorotrichloromethane and                                                                          to 100                                                difluorodichloromethane 2:3                                                    ______________________________________                                    

The suspension is poured into a conventional aerosol container with a metering valve. Preferably, 50 μl of suspension are dispensed on each actuation. The active substance may also be dispensed in a higher dosage if desired (e.g. 0.02% by weight).

2. Tablets

    ______________________________________                                         Active substance according to                                                                      0.05                                                       the invention                                                                  Colloidal silica    0.95                                                       Lactose             65.00                                                      Potato starch       28.00                                                      Polyvinylpyrrolidone                                                                               3.00                                                       Na-cellulose glycolate                                                                             2.00                                                       Magnesium stearate  1.00                                                       ______________________________________                                    

The ingredients are processed in the usual way to form tablets weighing 200 mg.

The advantageous properties of the new compounds are found for example in their inhibition of broncholysis in rabbits (acetylcholine spasm i.v.). After intravenous administration of the new active substances (dosage 3 μg/kg i.v.) the maximum effect was obtained after 10 to 40 minutes. Even on isolated organs, e.g. on the guinea-pig ileum or rectum, numerous compounds according to the invention were found to have a long duration of activity.

The new compounds may be prepared by methods known per se.

1. Preferably an ester of formula

    Z--CO--OR"                                                 (VII),

wherein Z is as hereinbefore defined and R" represents a C₁₋₄ -alkyl group, preferably methyl or ethyl, is transesterified, in the presence of a conventional transesterification catalyst, with an aminoalcohol of formula ##STR9## whereim m and n are as hereinbefore defined, Q'_(a) represents NR' or NH, Q_(a) has the same meaning as Q, with the proviso that if Q_(a) represents --CH₂ --Q"--(CH₂)_(p) --, Q" can only represent NR', and wherein the OH-group is in the α- and β-position, or

2. a reactive derivative (R'" represents a readily cleavable group) of the acid Z--CO--OH, particularly an acid chloride or imidazolide thereof, is reacted with an alcohol of formula VIII, optionally in excess or in the presence of a tertiary amine such as triethylamine, and optionally the resulting compound

a) if Q' represents NR' is quaternised with a reactive monoderivative X--R of a corresponding alkane (X=leaving group) or

b) if Q' represents NH is quaternised with a terminally disubstituted alkane X--(C₄₋₆ -alkylene)-X without intermediate isolation or

c) if Q_(a) equals --CH₂ --NE'--(CH₂)_(p) --, is quaternised with a reactive monoderivative X--R.

Alternatively, starting compounds may be quaternised, in which the starting compound VIII contains R representing a "halo- or hydroxy-substituted alkyl group" instead of R' at the nitrogen atom.

The transesterification according to process 1 is carried out with heating in an organic solvent, e.g. toluene, xylene or heptane, or in a melt, using strong bases such as sodium methoxide, sodium ethoxide, sodium hydride or metallic sodium as catalyst. In order to eliminate the lower alcohol released from the equilibrium, reduced pressure is used, and possibly the alcohol is distilled off azeotropically. The transesterification is carried out at temperatures generally not exceeding 95° C. Frequently, transesterification proceeds more easily in a melt. The reaction according to process 2 is carried out in an organic solvent or mixture of solvents which is sufficiently inert under the reaction conditions, e.g. acetone or acetonitrile, at temperatures between about 0° C. and the boiling temperature of the reaction mixture.

The free bases may be obtained from acid addition salts of the tertiary amines, if desired, using suitable basic compounds in a manner known per se. The quaternisation is carried out in suitable solvents, e.g. acetonitrile or acetonitrile/methylene chloride, preferably at ambient temperature; the preferred quaternising reagent is a corresponding alkyl halide, e.g. alkyl bromide, or a corresponding sulphonic acid derivative, e.g. a methane- or toluenesulphonic acid derivative. Transesterification products wherein Q' represents NH are used as starting materials for those compounds in which R and R' together represent a C₄₋₆ -alkylene group. Conversion into the tertiary and then quaternary compound is carried out using suitable 1,4-, 1,5- or 1,6-dihaloalkanes without intermediate isolation.

The starting compounds, where they have not already been described, may be obtained analogously to known compounds.

Examples:

Methyl di-(2-thienyl)glycolate from dimethyloxalate and 2-thienylmagnesium bromide;

Ethyl di-(2-thienyl)glycolate from (2-thienyl)glyoxylic acid and 2-thienyllithium;

Ethyl hydroxyphenyl-(2-thienyl)acetate from methylphenylglyoxylate and 2-thienylmagnesium bromide or from methyl (2-thienyl)glyoxylate and phenylmagnesium bromide

Similarly, methyl 2-thienylglyoxylate and cyclohexyl- or cyclopentylmagnesium bromide may be reacted.

There are also several possible methods of preparing the aminoalcohols.

Pseudoscopine can be obtained according to M. Polonovski et al., Bull. soc. chin. 43, 79 (1928).

Pseudotropenol can be isolated from the mixture (by fractional crystallisation or distillation) which is obtained, for example, according to V. Hayakawa et al., J. Amer. Chem. Soc. 1978, 100(6), 1786 or R. Noyori et al., J. Amer. Chem. Soc. 1974, 96(10), 3336.

N-ethylnorscopine and N-isopropylnorscopine may be prepared by hydrogenolysis from the corresponding N-alkylnorscopolamines analogously to Banholzer DE-A P 3215933.6-methyl-6-azabicyclo[3.2.1]octan-3-α-ol can be prepared according to F. I. Carroff et al., J. Med. Chem. 30, 805 (1987), and 7-methyl-7-azabicyclo-[2.2.1]heptan-2α-ol may be obtained according to J. R. Pfister et al., J. Pharmac. Sciences 74, 208 (1985).

Starting from 2- or 3-furylglyoxylnitrile the corresponding methylesters may be prepared in conventional manner via the 2- or 3-furylglyoxylic acid obtainable from the starting material. From these methylesters, the corresponding glycolic acid esters may be obtained as described with the organometallic derivatives of 2- or 3-bromothiophene. The organometallic compounds obtainable from 2-, 3- or 4-halopyridine can be reacted with methyl 2- or 3-thienylglyoxylate to obtain the corresponding glycolic acid esters.

Thienylglycolic acid esters in which the thiophene ring in the 2- or 3-position contains fluorine may be obtained, for example, starting from 2-fluorothiophene or 3-fluorothiophene (bromination to obtain 2-bromo-3-fluoro- or 2-bromo-5-fluorothiophene and, after conversion into corresponding organometallic compounds, reaction with suitable glyoxylic acid esters to obtain the glycolic acid esters.

2-fluorothiophene and 3-fluorothiophene may be reacted analogously to. Unterhalt, Arch. Pharm. 322, 839 (1989) to obtain the corresponding glyoxylic acid esters which may then in turn be reacted with 2- or 3-thienyl derivatives, for example, to obtain glycolic acid esters, as described above. By a suitable choice of components, symmetrically substituted dithienylglycolic acid esters may be prepared analogously.

A method analogous to benzoin condensation and benzylic acid rearrangement is also possible.

The acid chlorides required may be obtained from the acids and thionyl chloride whilst the imidazolides may be obtained from the acids and carbonyldimidazole.

The following Examples illustrate the invention without restricting it.

EXAMPLE 1

Benzylic acid scopine ester-methobromide

a) Benzylic acid scopine ester from α-chlorodiphenylacetic acid chloride and scopine

26.5 g (0.1 mol) α-chlorodiphenylacetic acid chloride are added to a solution of 31.0 g (0.2 mol) of scopine in 60 ml of anhydrous pyridine at 0° C. within 50 minutes with stirring. After it has all been added the mixture is stirred for 4 hours without cooling and then left to stand for 24 hours. In order to work up the mixture the scopine hydrochloride precipitated is suction filtered. The solution separated off is evaporated down under reduced pressure, the residue is dissolved in a mixture of 600 ml of water and 15 ml of conc. hydrochloric acid and heated to about 80° C. for 10 minutes. At a temperature below 20° C., sodium carbonate is added until a pH of 9 is achieved. The benzylic acid scopine ester is extracted with methylene chloride and the extracts are dried over sodium sulphate. After evaporation and treatment with acetone, white crystals are obtained, m.p. 182°-3° C. (decomp.), yield 31.8 g (87% of theory). Elementary analysis and spectra confirm that the title compound has been obtained which can be converted in the usual way into the hydrochloride, m.p. 256° C. (decomp.; from ethanol).

b) Benzylic acid scopine ester from benzylic acid imidazolide and scopine

A suspension of 7.13 g (0.046 mol) of scopine and 3.2 g (0.0115 mol) of benzylic acid imidazolide in 50 ml of acetone is heated to boiling point. After about 10 minutes a further 9.6 g (0.0345 mol) of benzylic acid imidazolide are gradually added thereto. After the reaction has ended the mixture is cooled with ice/common salt. The crystals precipitated are suction filtered. They may be converted into the hydrochloride, m.p. 256° C. (decomp.; from ethanol). Yield 8.9 g, 53% of theory).

c) Benzylic acid scopine ester methobromide

7.12 g (0.075 mol) of methylbromide dissolved in acetone are added to a suspension of 5.48 g (0.015 mol) of benzylic acid scopine ester in 120 ml of acetonitrile and 20 ml of carbon tetrachloride and the mixture is left to stand under a slight overpressure until the reaction has ended. The crystals precipitated are suction filtered, washed with cold acetonitrile then with diethylether and after drying (at 40° C. under reduced pressure) recrystallised from methanol/ether, m.p. 200° C. (decomp.). Elementary analysis and spectrum confirm that the desired compound has been obtained.

EXAMPLE 2

1-N-β-Fluoroethylnorscopolamine-methobromide

a) 1-N-β-Fluoroethylnorscopolamine-hydrochloride

A mixture of 16.3 (0.05 mol) of 1-norscopolamine-hydrochloride, 6.3 g (0.05 mol) of 2-bromo-fluoroethane, 10.6 g (0.1 mol) of sodium carbonate and 100 ml of acetonitrile is refluxed for 6 hours. Then a further 6.3 g (0.05 mol) of 2-bromofluoroethane and 5.3 g (0.05 mol) of sodium carbonate are added and the mixture is heated for a further 24 hours. Finally, 3.2 g (0.025 mol) of 2-bromofluoroethane and 2.7 g (0.025 mol) of sodium carbonate are added and the mixture is heated for a further 48 hours. It is suction filtered and the solution is concentrated by evaporation. The residue is taken up in methylene chloride, extracted with water and the methylene chloride phase is dried over sodium sulphate. After distillation of the methylene chloride an oily residue is obtained which is reacted in the usual way to form the hydrochloride. From methanol/ether 13.1 g of white crystals are obtained (70.4% of theory), m.p. 197°-8° C. (decomp.).

b) Reaction to form the methobromide

7.0 g (0.021 mol) of the amine liberated in the usual way from the hydrochloride obtained in a) are reacted in 20 ml of absolute acetonitrile with 9.9 g (0.104 mol) of methylbromide for 6 days under a slight overpressure. The crystals precipitated are recrystallised from methanol/ether. 3.9 g of white crystals, m.p. 194° C. (decomp.). Elementary analysis and spectra confirm that the title compound has been obtained.

EXAMPLE 3

Mandelic acid scopine ester methobromide

155.2 g (1.0 mol) of scopine are dissolved in 200 ml of absolute methylene chloride and 116.9 g (0.55 mol) of acetylmandelic acid chloride dissolved in 100 ml of absolute methylene chloride are added dropwise thereto (at 20° C. within 1 hour). (The acetylmandelic acid chloride is obtained from acetylmandelic acid and thionyl chloride). After one hour the scopine hydrochloride precipitated is separated off, the methylene chloride solution is extracted with water and dried.

The combined aqueous phases are made alkaline with sodium carbonate, extracted with methylene chloride and the methylene chloride phase is dried. The solvent is distilled off from the combined methylene chloride solutions. The base which remains is converted into the hydrochloride in the usual way. After recrystallisation from acetonitrile, 124.6 g (67.7% of theory) of white crystals are obtained, m.p. 207° C. (decomp.).

27.5 g (0.075 mol) of the acetyl compound thus obtained are left to stand in 110 ml of 20% hydrochloric acid for 20 hours at ambient temperature. Whilst cooling, the reaction solution is made alkaline and the mandelic acid scopine ester is extracted with methylene chloride. After drying over sodium sulphate and distillation of the solvent, the hydrochloride is prepared in the usual way. From methanol/ether, 22.5 g (92.4% of theory) of white crystals are obtained, m.p. 141°-2° C. 10.7 g (0.037 mol) of the ester liberated from the hydrochloride in the usual way are left to stand for 40 hours in acetonitrile with 17.58 g (0.185 mol) of methylbromide under a slight overpressure.

The crystals precipitated are suction filtered, washed with cold acetonitrile and recrystallised from methanol/ether. 10.0 g (70.4% of theory) of white crystals are obtained, m.p. 223° C. (decomp.).

Elementary analysis and spectra confirm that the title compound has been obtained.

EXAMPLE 4

Xanthene-9-carboxylic acid scopine ester methobromide

a) At 20° C., a solution of 11.1 g (0.11 mol) of triethylamine in 20 ml of acetone and 26.9 g (0.11 mol) of xanthene-9-carboxylic acid chloride (obtained from xanthene-9-carboxylic acid and thionyl chloride) in 80 ml of acetone are simultaneously added dropwise to a solution of 15.5 g (0.01 mol) of scopine in 50 ml of acetone at 20° C. After 4 hours a further 1.1 g (0.01 mol) of triethylamine and 2.69 (0.011 mol) of xanthene-9-carboxylic acid chloride are added. After 4 days the mixture is suction filtered and the solvent is distilled off from the solution. Sodium carbonate solution is added to the residue and extracted with methylene chloride. The organic phase is dried over sodium sulphate and the solvent is distilled off. From the residue, the hydrochloride of the resulting xanthene-9-carboxylic acid scopine ester is obtained in the conventional manner; white crystals from acetonitrile/ether, m.p. 223° C. (decomp.); yield 21.8 g.

b) The base is liberated in the usual way from a sufficient quantity of the hydrochloride obtained in a). 36.3 g (0.1 mol) thereof are reacted in a solution of 47.5 g (0.5 mol) of methylbromide in 49 g of acetonitrile for 24 hours under slight overpressure. The crystals obtained are suction filtered, washed with acetone/ether and recrystallised from ethanol. Yield 44.0 g (95.8% of theory), white crystals, m.p. 139° C. The crystals contain 0.5 mol of ethanol. Elementary analysis and spectra confirm the presence of the title compound.

The other compounds according to the invention may also be obtained in accordance with the Examples given above. The compounds melt with decomposition.

                  TABLE I                                                          ______________________________________                                         Compounds of formula                                                            ##STR10##                                                                     No.   R.sub.1 A                     M.p. [°C.]                          ______________________________________                                         1     OH      3α-Tropanyl-methobromide                                                                       275-6                                      2     OH      3α-Tropanyl-β-fluorethobromide                                                            205-6                                      3     H       3α-N-Ethyl-(6β,7β-Epoxy)-                                                            228                                                      nortropanyl-methobromide                                         4     H       3α-N-Propyl-(6β,7β-Epoxy)-                                                           206-7                                                    nortropanyl-methobromide                                         5     H       3α-N-Isopropyl-(6β,7β-Epoxy)-                                                        218                                                      nortropanyl-methobromide                                         6     H       3α-(6β,7β-Epoxy)-                                                                    207                                                      tropanyl-methobromide                                            7     H       3α-(6, 7-Dehydro)tropanyl-                                                                     226-8                                                    methobromide                                                     8     H       3α-Tropanyl-methobromide                                                                       275-6                                      9     H       3α-N-Ethyl-nortropanyl-methobromide                                                            256-7                                      10    H       (-)-3α-N-Isopropylnortropanyl-                                                                 256                                                      methobromide                                                     11    H       (+)-3α-N-Isopropylnortropanyl-                                                                 256                                                      methobromide                                                     12    H       3α-Nortropanyl-8,1'-                                                                           267-70                                                   pyrrolidinium-bromide                                            13    H       (+)-3α-Tropanyl-methobromide                                                                   278-81                                     14    H       (-)-3α-Tropanyl-methobromide                                                                   278-81                                     ______________________________________                                    

                  TABLE II                                                         ______________________________________                                         Compounds of formula                                                            ##STR11##                                                                     No.    R.sub.1  A                 M.p. [°C.]                            ______________________________________                                         1      OH       3α-N-Isopropylnortropanyl-                                                                 258                                                          methobromide                                                   2      OH       3α-N-β-Chlorethylnortropanyl-                                                         203                                                          methobromide                                                   3      OH       3α-N-Ethylnortropanyl-                                                                     269                                                          methobromide                                                   4      OH       3α-Tropanyl-ethobromide                                                                    258                                          5      OH       3α-(6β,7β-Epoxy)tropanyl-                                                        200                                                          methobromide                                                   6      OH       3α-N-Ethyl-(6β,7β-Epoxy)-                                                        220-1                                                        nortropanyl-methobromide                                       7      OH       3α-(6β,7β-Epoxy)-N-isopropyl                                                     234-5                                                        nortropanyl-methobromide                                       8      OH       3α-N-Methylgranatanyl-                                                                     249                                                          methobromide                                                   9      OH       3α-N-Isopropylgranatanyl-                                                                   219-20                                                      methobromide                                                   10     OH       3α-(6, 7-Dehydro)tropanyl-                                                                 207-8                                                        methobromide                                                   11     H        3α-(6, 7-Dehydro)tropanyl-                                                                 214-5                                                        methobromide                                                   12     OH       3α-(6, 7-Dehydro)-N-isopropyl-                                                             223                                                          nortropanyl-methobromide                                       13     H        3α-Nortropanyl-8,1'-                                                                       231-2                                                        pyrrolidinium-bromide                                          ______________________________________                                    

                  TABLE III                                                        ______________________________________                                         Compounds of formula                                                            ##STR12##                                                                     No.    R.sub.1  A                M.p. [C.°]                             ______________________________________                                         1      H        3α-(6β,7β-Epoxy)-tropanyl-                                                      213-4                                                         methobromide                                                   2      H        3α-(6β,7β-Epoxy)-tropanyl-                                                      204-5                                                         propargochloride                                               3      H        3α-N-Ethyl-(6β,7β-Epoxy)-                                                       201                                                           nortropanyl-methobromide                                       4      H        3α-(6, 7-Dehydro)tropanyl-                                                                238-9                                                         methobromide                                                   5      H        3α-Tropanyl-methobromide                                                                  203-5                                         6      OH       3α-(6β,7β-Epoxy)tropanyl-                                      metho-methanesulphonate                                        ______________________________________                                    

                  TABLE IV                                                         ______________________________________                                         Compounds of formula                                                            ##STR13##                                                                     No.    R.sub.1  A                   M.p. [°C.]                          ______________________________________                                         1      H        3α-(6β,7β-Epoxy)-N-n-propyl                                                        213-4                                                      nortropanyl-methobromide                                       2      H        3α-(6β,7β-Epoxy)-N-isopropyl-                                                      242                                                        nortropanyl-methobromide                                       3      H        3α-(6β,7β-Epoxy)-N-ethyl-                                                          217                                                        nortropanyl-methobromide                                       4      H        3α-(6β,7β-Epoxy)tropanyl-                                                          139                                                        methobromide (with crystal ether)                              5      H        3α-(6β,7β-Epoxy)tropanyl-                                                          128-31                                                     ethobromide                                                    6      H        3α-Tropanyl-ethobromide                                                                      212-3                                      7      OH       3α-N-Isopropylnortropanyl-                                                                   229-32                                                     metho-methanesulphonate                                        8      H        3α-N-Isopropylnortropanyl-                                                                   184-5                                                      methobromide                                                   9      H        3α-(6,7-Dehydro)-N-isopropyl-                                                                259                                                        nortropanyl-methobromide                                       10     H        3α-(6,7-Dehydro)-tropanyl-                                                                   237-8                                                      methobromide                                                   ______________________________________                                    

                                      TABLE V                                      __________________________________________________________________________     Compounds of formula                                                            ##STR14##                                                                     No. R.sub.1                                                                               R.sub.2                                                                             W    A           M.p. [°C.]                             __________________________________________________________________________     1   OH     H    H    3α-(6β,7β-Epoxy)-                                                          223                                                                tropanyl-methobromide                                     2   CH.sub.2 OH                                                                           H    H    3α-(6β,7β-Epoxy)-                                                          190                                                                tropanyl-ethobromide                                      3   H      Cyclo-                                                                              H    3α-(6β,7β-Epoxy)-                                                          242                                                      heptyl    tropanyl-methobromide                                     4   H      Cyclo-                                                                              H    3α-(6β,7β-Epoxy)-                                                          215-6                                                    heptyl    tropanyl-propobromide                                     5   C.sub.5 H.sub.8                                                                            H    3α-(6β,7β-Epoxy)-                                                          223-4                                                              tropanyl-methobromide                                     6   CH.sub.2 OH                                                                           H    H    3α-(6β,7β-Epoxy)-N-                                                        194                                                                (β-fluorethyl)-nor-                                                       tropanyl-methobromide                                     7   CH.sub.2 OH                                                                           H    H    3α-(6β,7β-Epoxy)-N-                                                        211                                                                (β-hydroxyethyl)-                                                         nortropanyl-                                                                   methobromide                                              8   OH     C.sub.6 H.sub.4                                                                     4-F  3α-Tropanyl-,                                                                        220-1                                                              methobromide                                              9   C.sub.5 H.sub.8                                                                            H    3α-Tropanyl-                                                                         287-9                                                              methobromide                                              10  C.sub.5 H.sub.8                                                                            H    3α-N-Isopropyl-                                                                      263                                                                nortropanyl-                                                                   methobromide                                              11  C.sub.6 H.sub.10                                                                           H    3α-N-Isopropyl-                                                                      261                                                                nortropanyl-                                                                   methobromide                                              12  OH     C.sub.6 H.sub.11                                                                    H    3α-(6,7-Dehydro)-                                                                    233-5                                                              tropanyl-methobromide                                     13  H      C.sub.6 H.sub.11                                                                    3-CH.sub.3                                                                          3α-N-Isopropyl-                                                                      252-4                                                              nortropanyl-                                                                   methobromide                                              14  H      C.sub.5 H.sub.9                                                                     3-CH.sub.3                                                                          3α-Nortropanyl-                                                                      224-6                                                              8,1'-pyrrolidinium-                                                            bromide                                                   __________________________________________________________________________

                  TABLE VI                                                         ______________________________________                                         Compounds of formula                                                            ##STR15##                                                                     No.     A                   R.sub.1 M.p. [°C.]                          ______________________________________                                         1       3α-(6β,7β-Epoxy)-tropanyl-                                                         H       176                                                methobromide. H.sub.2 O                                                2       3α-Tropanyl-methobromide                                                                     H                                                  3       3α-(6,7-Dehydro)-tropanyl-                                                                   OH                                                         methobromide                                                           4       3α-(N-β-Fluorethyl)-nortropanyl-                                                        H                                                          methobromide                                                           5       3α-Tropanyl-β-fluorethobromide                                                          OH                                                 6       3α-(N-Isopropyl)-granatanyl-                                                                 H                                                          methobromide                                                           7       3α-(N-Isopropyl)-nortropanyl-                                                                H                                                          methobromide                                                           8       3α-(6β,7β-Epoxy)-N-isopropyl-                                                      OH                                                         nortropanyl-methobromide                                               9       3α-(6β,7β-Epoxy)-N-ethylnor-                                                       OH                                                         tropanyl-methobromide                                                  10      3α-(N-Ethyl)-nortropanyl-                                                                    OH                                                         methobromide                                                           11      3α-(N-Methyl)-granatanyl-                                                                    CH.sub.3                                                   methobromide                                                           ______________________________________                                    

                  TABLE VII                                                        ______________________________________                                         Compounds of formula                                                            ##STR16##                                                                     No.     A                 R.sub.1 M.p. [°C.]                            ______________________________________                                         1       3α-(6β,7β-Epoxy)-tropanyl-                                                       H                                                            methobromide                                                           2       3α-(6,7-Dehydro)-tropanyl-                                                                 H                                                            methobromide                                                           3       3α-(6β,7β-Epoxy)-tropanyl-                                                       Methyl                                                       methobromide                                                           4       3α-(6,7-Dehydro)-tropanyl-                                                                 Methyl                                                       methobromide                                                           5       3α-(6β,7β-Epoxy)-tropanyl-                                                       OH                                                           methobromide                                                           6       3α-(6,7-Dehydro)-tropanyl-                                                                 OH                                                           methobromide                                                           ______________________________________                                    

                  TABLE VIII                                                       ______________________________________                                         Compounds of formula                                                            ##STR17##                                                                     No.   A                 R.sub.2   M.p. [°C.]                            ______________________________________                                         1     3α-(6β,7β-Epoxy)-tropanyl-                                                       Phenyl                                                       methobromide                                                             2     3α-(6,7-Dehydro)-tropanyl-                                                                 Phenyl                                                       methobromide                                                             3     3α-(6β,7β-Epoxy)-tropanyl-                                                       Cyclopentyl                                                  methobromide                                                             4     3α-(6,7-Dehydro)-tropanyl-                                                                 3-Thienyl                                                    methobromide                                                             5     3α-Tropanyl-methobromide                                                                   3-Thienyl                                              6     3α-(N-Methyl)-granatanyl-                                                                  3-Thienyl                                                    methobromide                                                             ______________________________________                                    

                  TABLE IX                                                         ______________________________________                                         Compounds of formula                                                            ##STR18##                                                                     No.   A                 R.sub.2   M.p. [°C.]                            ______________________________________                                         1     3α-(6β,7β-Epoxy)-tropanyl-                                                       Phenyl                                                       methobromide                                                             2     3α-(6,7-Dehydro)-tropanyl-                                                                 Phenyl                                                       methobromide                                                             3     3α-(6β,7β-Epoxy)-tropanyl-                                                       Cyclopentyl                                                  methobromide                                                             4     3α-(6,7-Dehydro)-tropanyl-                                                                 3-Thienyl                                                    methobromide                                                             5     3α-Tropanyl-methobromide                                                                   3-Thienyl                                              6     3α-(N-Methyl)-granatanyl-                                                                  3-Thienyl                                                    methobromide                                                             ______________________________________                                    

                  TABLE X                                                          ______________________________________                                         Compounds of formula                                                            ##STR19##                                                                     No.     A                 R.sub.1 M.p. [°C.]                            ______________________________________                                         1       3α-(6β,7β-Epoxy)-tropanyl-                                                       H                                                            methobromide                                                           2       3α-(6,7-Dehydro)-tropanyl-                                                                 H                                                            methobromide                                                           3       3α-(6β,7β-Epoxy)-tropanyl-                                                       Methyl                                                       methobromide                                                           4       3α-(6,7-Dehydro)-tropanyl-                                                                 Methyl                                                       methobromide                                                           5       3α-(6β,7β-Epoxy)-tropanyl-                                                       OH                                                           methobromide                                                           6       3α-(6,7-Dehydro)-tropanyl-                                                                 OH                                                           methobromide                                                           ______________________________________                                    

                  TABLE XI                                                         ______________________________________                                         Compounds of formula                                                            ##STR20##                                                                     No.       A                M.p. [°C.]                                   ______________________________________                                         1         3α-(6β,7β-Epoxy)-tropanyl-                                     methobromide                                                         2         3α-(6,7-Dehydro)-tropanyl-                                               methobromide                                                         3         3α-(6β,7β-Epoxy)-tropanyl-                                     ethobromide                                                          4         3α-(6,7-Dehydro)-tropanyl-                                               ethobromide                                                          5         3α-Tropanyl                                                              methobromide                                                         6         3α-(N-Methyl)-granatanyl-                                                methobromide                                                         ______________________________________                                    

                  TABLE XII                                                        ______________________________________                                         Compounds of formula                                                            ##STR21##                                                                     No.       A                M.p. [°C.]                                   ______________________________________                                         1         3α-(6β,7β-Epoxy)-tropanyl-                                     methobromide                                                         2         3α-(6,7-Dehydro)-tropanyl-                                               methobromide                                                         3         3α-(6β,7β-Epoxy)-tropanyl-                                     ethobromide                                                          4         3α-(6,7-Dehydro)-tropanyl-                                               ethobromide                                                          5         3α-Tropanyl                                                              methobromide                                                         6         3α-(N-Methyl)-granatanyl-                                                methobromide                                                         ______________________________________                                    

                  TABLE XIII                                                       ______________________________________                                         Compounds of formula                                                            ##STR22##                                                                     No.       A                M.p. [°C.]                                   ______________________________________                                         1         3α-(6β,7β-Epoxy)-tropanyl-                                     methobromide                                                         2         3α-(6,7-Dehydro)-tropanyl-                                               methobromide                                                         3         3α-(6β,7β-Epoxy)-tropanyl-                                     ethobromide                                                          4         3α-(6,7-Dehydro)-tropanyl-                                               ethobromide                                                          5         3α-Tropanyl                                                              methobromide                                                         6         3α-(N-Methyl)-granatanyl-                                                methobromide                                                         ______________________________________                                    

                  TABLE XIV                                                        ______________________________________                                         Quarternary compounds of formula                                                ##STR23##                                                                     No.   A                   R.sub.2   M.p. [°C.]                          ______________________________________                                         1     3α-(6β,7β-Epoxy)-tropanyl-                                                         2-Thienyl                                                  methobromide                                                             2     3α-Tropanyl-methobromide                                                                     2-Thienyl                                            3     3α-(6,7-Dehydro)-tropanyl-                                                                   2-Thienyl                                                  methobromide                                                             4     3α-(N-β-Fluorethyl)-nortropanyl-                                                        2-Thienyl                                                  methobromide                                                             5     3α-Tropanyl-β-fluorethobromide                                                          2-Thienyl                                            6     3α-(N-Isopropyl)-granatanyl-                                                                 2-Thienyl                                                  methobromide                                                             7     3α-(N-Isopropyl)-nortropanyl-                                                                2-Thienyl                                                  methobromide                                                             8     3α-(6β,7β-Epoxy)-N-isopropyl-                                                      2-Thienyl                                                  nortropanyl-methobromide                                                 9     3α-(6β,7β-Epoxy)-N-ethylnor-                                                       2-Thienyl                                                  tropanyl-methobromide                                                    10    3α-(N-Ethyl)-nortropanyl-                                                                    2-Thienyl                                                  methobromide                                                             11    3α-(N-Methyl)-granatanyl-                                                                    2-Thienyl                                                  methobromide                                                             12    3α-(6β,7β-Epoxy)-N-β-fluoroethyl-                                             2-Thienyl                                                  nortropanyl-methobromide                                                 13    3α-(6β,7β-Epoxy)-N-n-propyl-                                                       2-Thienyl                                                  nortropanyl-methobromide                                                 14    3α-Tropanyl-β-hydroxyethobromide                                                        2-Thienyl                                            15    3α-(6β,7β-Epoxy)-tropanyl-                                                         Phenyl                                                     methobromide                                                             16    3α-Tropanyl-methobromide                                                                     Phenyl                                               17    3α-(N-β-Fluoroethyl)-                                                                   Phenyl                                                     nortropanyl-methobromide                                                 18    3α-(6,7-Dehydro)-tropanyl-                                                                   Phenyl                                                     methobromide                                                             19    3α-(N-Ethyl)-nortropanyl-                                                                    Phenyl                                                     methobromide                                                             20    3α-(N-Isopropyl)-nortropanyl-                                                                Phenyl                                                     methobromide                                                             21    3α-Tropanyl-ethobromide                                                                      Phenyl                                               22    3α-(N-Ethyl)-nortropanyl-                                                                    Phenyl                                                     ethobromide                                                              23    3α-(6β,7β-Epoxy)-tropanyl-                                                         Phenyl                                                     ethobromide                                                              24    3α-Tropanyl-β-fluorthobromide                                                           Phenyl                                               25    3α-Tropanyl-methobromide                                                                     Cyclohexyl                                           26    3α-(N-β-Fluorethyl)-nortropanyl-                                                        Cyclohexyl                                                 methobromide                                                             27    3α-Tropanyl-β-fluorethobromide                                                          Cyclohexyl                                           28    3α-Tropanyl-methobromide                                                                     Cyclopentyl                                          29    3α-Tropanyl-ethobromide                                                                      Cyclopentyl                                          30    3α-(N-Ethyl)-nortropanyl-                                                                    Cyclopentyl                                                methobromide                                                             31    3α-(N-Isopropyl)-nortropanyl-                                                                Cyclopentyl                                                methobromide                                                             32    3α-Tropanyl-β-fluorethobromide                                                          Cyclopentyl                                          33    3α-(N-β-Fluorethyl)-nortropanyl-                                                        Cyclopentyl                                                methobromide                                                             34    3α(6,7-Dehydro)-tropanyl-                                                                    2-Thienyl                                                  metho-methanesulphonate                                                  35    3β-(6β,7β-Epoxy)-tropanyl-                                                          2-Thienyl                                                  methobromide                                                             36    3β-Tropanyl-methobromide                                                                      2-Thienyl                                            37    3β-(6,7-Dehydro)-tropanyl-                                                                    2-Thienyl                                                  methobromide                                                             38    3α(6,7-Dehydro)-tropanyl-                                                                    3-Thienyl                                                  methobromide                                                             39    3α-(6β,7β-Epoxy)-tropanyl-                                                         3-Thienyl                                                  methobromide                                                             40    (+)-Enantiomer of No. 1                                                  41    (-)-Enantiomer of No. 1                                                  42    3α-(6β,7β-Epoxy)-tropanyl-                                                         2-Furyl                                                    methobromide                                                             43    3α-(6,7-Dehydro)-tropanyl-                                                                   2-Furyl                                                    methobromide                                                             44    3α-Tropanyl-methobromide                                                                     2-Furyl                                              45    3α-(6β,7β-Epoxy)-tropanyl                                                          2-Pyridyl                                                  methobromide                                                             46    3α-(6,7-Dehydro)-tropanyl                                                                    2-Pyridyl                                                  methobromide                                                             47    3α-Tropanyl-methobromide                                                                     2-Pyridyl                                            48    3α-Tropanyl-methobromide                                                                     3-Thienyl                                            49    3α-(6,7-Dehydro)-tropanyl                                                                    Cyclopentyl                                                methobromide                                                             50    3α-(6β,7β-Epoxy)-tropanyl                                                          Cyclohexyl                                                 methobromide                                                             51    3α-(6,7-Dehydro)-tropanyl                                                                    Cyclohexyl                                                 methobromide                                                             52    3α-(6β,7β-Epoxy)-tropanyl                                                          Cyclopentyl                                                methobromide                                                             ______________________________________                                    

                  TABLE XV                                                         ______________________________________                                         Compounds of formula                                                            ##STR24##                                                                     No.  A                R.sub.2     R.sub.a M.p [°C.]                     ______________________________________                                         1    3α-(6β,7β-Epoxy)-tropanyl-                                                      2-Thienyl   5-Methyl                                          methobromide                                                              2    3α-(6,7-Dehydro)-tropanyl-                                                                2-Thienyl   5-Methyl                                          methobromide                                                              3    3α-Tropanyl-methobromide                                                                  2-Thienyl   5-Methyl                                     4    3α-(6β,7β-Epoxy)-tropanyl-                                                      2-(5-Methyl)-                                                                              5-Methyl                                          methobromide     thienyl                                                  5    3α-(6,7-Dehydro)-tropanyl-                                                                2-(5-Methyl)-                                                                              5-Methyl                                          methobromide     thienyl                                                  6    3α-Tropanyl-methobromide                                                                  2-(5-Methyl)-                                                                              5-Methyl                                                           thienyl                                                  7    3α-(6β,7β-Epoxy)-tropanyl-                                                      2-Thienyl   5-Fluoro                                          methobromide                                                              8    3α-(6,7-Dehydro)-tropanyl-                                                                2-Thienyl   5-Fluoro                                          methobromide                                                              9    3α-Tropanyl-methobromide                                                                  2-Thienyl   5-Fluoro                                     10   3α-(6β,7β-Epoxy)-tropanyl-                                                      2-(5-Fluoro)-                                                                              5-Fluoro                                          methobromide     thienyl                                                  11   3α-(6,7-Dehydro)-tropanyl-                                                                2-(5-Fluoro)-                                                                              5-Fluoro                                          methobromide     thienyl                                                  12   3α-Tropanyl-methobromide                                                                  2-(5-Fluoro)-                                                                              5-Fluoro                                                           thienyl                                                  ______________________________________                                    

                  TABLE XVI                                                        ______________________________________                                         Compounds of formula                                                            ##STR25##                                                                     No.     A                R.sub.2   M.p. [°C.]                           ______________________________________                                         1       3α-(6β,7β-Epoxy)-tropanyl                                                       Phenyl                                                        methobromide                                                           2       3α-(6,7-Dehydro)-tropanyl                                                                 Phenyl                                                        methobromide                                                           3       3α-(6β,7β-Epoxy)-tropanyl                                                       3-Thienyl                                                     methobromide                                                           4       3α-(6,7-Dehydro)-tropanyl                                                                 3-Thienyl                                                     methobromide                                                           5       3α-Tropanyl                                                                               3-Thienyl                                                     methobromide                                                           6       3α-(N-Methyl)-granatanyl                                                                  3-Thienyl                                                     methobromide                                                           ______________________________________                                    

                  TABLE XVII                                                       ______________________________________                                         Compounds of formula                                                            ##STR26##                                                                     No.      A                     M.p. [°C.]                               ______________________________________                                         1        3α-(6β,7β-Epoxy)-tropanyl-                                     methobromide                                                          2        3α-Tropanyl-methobromide                                        3        3α-(6,7-Dehydro)-tropanyl-                                               methobromide                                                          4        3α-(N-β-Fluorethyl)-nortropanyl-                                    methobromide                                                          5        3α-Tropanyl-β-fluorethobromide                             6        3α-(N-Isopropyl)-granatanyl-                                             methobromide                                                          7        3α-(N-Isopropyl)-nortropanyl-                                            methobromide                                                          8        3α-(6β,7β-Epoxy)-N-isopropyl-                                  nortropanyl-methobromide                                              9        3α-(6β,7β-Epoxy)-N-ethylnor-                                   tropanyl-methobromide                                                 10       3α-(N-Ethyl)-nortropanyl-                                                methobromide                                                          11       3α-(N-Methyl)-granatanyl-                                                methobromide                                                          12       3α-(6β,7β-Epoxy)-N-β-fluoroethyl-                         nortropanyl-methobromide                                              13       3α-(6β,7β-Epoxy)-N-n-Propyl-                                   nortropanyl-methobromide                                              14       3α-Tropanyl-β-hydroxyethobromide                           15       3α(6,7-Debydro)-tropanyl-                                                metho-methanesulphonate                                               16       3β-(6β,7β-Epoxy)-tropanyl-                                      methobromide                                                          17       3β-Tropanyl-methobromide                                         18       3β-(6,7-Dehydro)-tropanyl-                                                methobromide                                                          ______________________________________                                    

                  TABLE XVIII                                                      ______________________________________                                         Compounds of formula                                                            ##STR27##                                                                     No.      A                R.sub.1  M.p. [°C.]                           ______________________________________                                         1        3α-(6β,7β-Epoxy)-tropanyl                                                       OH                                                            methobromide                                                          2        3α-(6,7-Dehydro)-tropanyl                                                                 OH                                                            methobromide                                                          3        3α-(6β,7β-Epoxy)-tropanyl                                                       Methyl                                                        methobromide                                                          4        3α-(6,7-Dehydro)-tropanyl                                                                 Methyl                                                        methobromide                                                          5        3α-Tropanyl                                                                               H                                                             methobromide                                                          6        3α-(N-Ethyl)-nortropanyl                                                                  H                                                             methobromide                                                          ______________________________________                                    

                  TABLE A                                                          ______________________________________                                         Compounds of formula                                                            ##STR28##                                                                                                           Mp.[C.°]                                                                Hydro-                                   No.   A               R.sub.2   Base  chloride                                 ______________________________________                                          1    3α-(6β,7β-Epoxy)-tropanyl                                                      2-Thienyl 149-50                                                                               238-41                                    2    3α-Tropanyl                                                                              2-Thienyl 167-8 253                                       3    3α-(6,7-Dehydro)-tropanyl                                                                2-Thienyl 164-5                                           4    3α-(N-β-Fluorethyl)-                                                                2-Thienyl       236                                            nortropanyl                                                               5    3α-(N-Isopropyl)-                                                                        2-Thienyl       232                                            granatanyl                                                                6    3α-(N-Isopropyl)-                                                                        2-Thienyl       250                                            nortropanyl                                                               7    3α-(6β,7β-Epoxy)-N-iso-                                                        2-Thienyl       206                                            propylnortropanyl                                                         8    3α-(6β,7β-Epoxy)-N-ethyl-                                                      2-Thienyl       212-3                                          nortropanyl                                                               9    3α-(N-Ethyl)-nortropanyl                                                                 2-Thienyl       256-7                                    10    3α-(N- Methyl)-granatanyl                                                                2-Thienyl       241                                      11    3α-(6β,7β-Epoxy)-N-β-                                                     2-Thienyl       188-90                                         fluorethylnortropanyl                                                    12    3α-(6β,7β-Epoxy)-N-n-                                                          2-Thienyl 104-6                                                propylnortropanyl                                                        13    3α-(6β,7β-Epoxy)-N-n-                                                          2-Thienyl       225-7                                          butylnortropanyl                                                         14    3α-(6β,7β-Eboxy)-tropanyl                                                      Phenyl          246-7                                    15    3α-Tropanyl                                                                              Phenyl          243-4                                    16    3α-(N-β-Fluoroethyl)-                                                               Phenyl          219-20                                         nortropanyl                                                              17    3α-(6,7-Dehydro)-tropanyl                                                                Phenyl    181-3                                          18    3α-(N-Ethyl)-nortropanyl                                                                 Phenyl          231-2                                    19    3α-(N-Isopropyl)-                                                                        Phenyl          246-7                                          nortropanyl                                                              20    3α-Tropanyl                                                                              Cyclohexyl      260                                      21    3α-(N-β-Fluoroethyl                                                                 Cyclohexyl      203-4                                          nortropanyl                                                              22    3α-(6β,7β-Epoxy)-tropanyl                                                      Cyclopentyl     237                                      23    3α-Tropanyl                                                                              Cyclopentyl     260                                      24    3α(N-β-Fluoroethyl)-                                                                Cyclopentyl     182-3                                          nortropanyl                                                              25    3α-(N-Ethyl)-nortropanyl                                                                 Cyclopentyl     227-8                                    26    3α-(N-Isopropyl)-                                                                        Cyclopentyl     174-5                                          nortropanyl                                                              27    3β-(6β,7β-Epoxy)-tropanyl                                                       2-Thienyl       240-2                                    28    3β-Tropanyl                                                                               2-Thienyl       217-9                                    29    3β-(6,7-Dehydro)-tropanyl                                                                 2-Thienyl       233-5                                    30    3α-(6,7-Dehydro)-tropanyl                                                                3-Thienyl       247-8                                    31    3α-(6β,7β-Epoxy)-tropanyl                                                      3-Thienyl       242-3                                    32    3α-(6β,7β-Epoxy)-tropanyl                                                      2-Furyl                                                  33    3α-(6,7-Dehydro)-tropanyl                                                                2-Furyl                                                  34    3α-Tropanyl                                                                              2-Furyl                                                  35    3α-Tropanyl                                                                              2-Pyridyl                                                36    3α(6β,7β-Epoxy)-tropanyl                                                       2-Pyridyl                                                37    3α-(6,7-Dehydro)-tropanyl                                                                2-Pyridyl                                                38    3α-Tropanyl                                                                              3-Thienyl                                                39    3α-(6,7-Dehydro)-tropanyl                                                                Cyclopentyl                                              40    3α-(6β,7β-Epoxy)-tropanyl                                                      Cyclohexyl                                               41    3α-(6,7-Dehydro)-tropanyl                                                                Cyclohexyl                                               ______________________________________                                          Note: all hydrochlorides melt with decomposition.                         

We claim:
 1. A compound of formula ##STR29## wherein R is an optionally halo- or hydroxy-substituted C₁₋₄ alkyl group;R' is a C₁₋₄ alkyl group; or R and R' together form a C4₋₆ alkylene group; X⁻ is an anion; and R₁ is H, OH, CH₂ OH, C₁₋₄ alkyl or C₁₋₄ alkoxy.
 2. The compound according to claim 1, wherein X⁻ is bromide.
 3. The compound according to claim 1, wherein R₁ is OH, CH₃ or CH₂ OH.
 4. The compound according to claim 1, wherein R is methyl and R' is methyl, ethyl, n-propyl or i-propyl.
 5. A pharmaceutical composition comprising a compound according to any one of claims 1-4 and a pharmaceutically acceptable excipient or carrier.
 6. A method for treating a disease which is responsive to an anti-cholinergic agent in a warm-blooded animal, comprising the step of administering to said animal a therapeutically effective amount of the pharmaceutical composition according to claim
 5. 7. A method for treating a respiratory tract disease in a warm-blooded animal, comprising the step of administering to said animal a therapeutically effective amount of the pharmaceutical composition according to claim
 6. 8. A method for treating sinus bradycardia in a warm-blooded animal, comprising the step of administering to said animal a therapeutically effective amount of the pharmaceutical composition according to claim
 6. 9. The method according to any one of claims 6-8, wherein said pharmaceutical composition is administered by inhalation.
 10. The method according to any one of claims 6-8, wherein said pharmaceutical composition is administered intravenously or orally. 